• Assess for signs of deep venous thrombosis and pulmonary edema (dyspnea, chest pain, arm or leg swelling) periodically during therapy; risk is greater when lenalidomide is administered with dexamethasone.
• Assess for skin rash. Discontinue lenalidomide if rash occurs; may cause SJS, DRESS, or TEN. Consider interruption or discontinuation for Grade 2-3 skin rash. Permanently discontinue lenalidomide for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN or DRESS.
• Monitor for signs and symptoms of tumor flare reaction (tender lymph node swelling, low-grade fever, pain rash) in patients with MCL; may mimic disease progression. Grade 1 and 2 tumor flare reaction (TFR): Lenalidomide may be continued in patients without interruption or modification, at health care professional's discretion. May also be treated with corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioid analgesics. Grade 3 or 4 TFR: withhold treatment with lenalidomide until TFR resolves to ≤ Grade 1. May be treated for management of symptoms per the guidance for treatment of Grade 1 and 2 TFR.

Lab Test Considerations:

• Verify negative pregnancy status before starting therapy. Pregnancy tests with a sensitivity of at least 50 mIU/mL must be done within 10–14 days and within 24 hrs of starting therapy. Once treatment has started, verify negative pregnancy tests weekly during first 4 wk of use, then every 4 wk in females with a regular menstrual cycle and every 2 wk in females with an irregular cycle.
  • Patients taking lenalidomide for multiple myeloma with dexamethasone or as maintenance therapy: Monitor CBC every 7 days for first 2 cycles, on days 1 and 15 of Cycle 3, and every 28 days thereafter. Patients taking lenalidomide for myelodysplastic syndrome: Monitor CBC with differential, platelet count, hemoglobin, and hematocrit weekly for first 8 wk of therapy and at least monthly thereafter. Patients taking lenalidomide for mantle cell lymphoma: Monitor CBC weekly for first 28 days, every 2 wk during Cycles 2–4, and monthly thereafter. May require dose interruption and/or reduction and use of blood support and/or growth factors.
  • May cause neutropenia with an onset of 42 days (range 4–411 days) and recovery time of 17 days (range 2–170 days). For multiple myeloma: starting dose is 25 mg/day—If neutropenia develops and neutrophils fall to <1000/mcL interrupt therapy, follow CBC weekly. When neutrophils return to ≥1000/mcL and neutropenia is the only toxicity, resume lenalidomide at 25 mg daily. If neutrophils return to ≥1000/mcL and if other toxicity, resume lenalidomide at next lower dose. For each subsequent drop <1000/mcL interrupt therapy. If neutrophils return to ≥1000/mcL, resume at next lower dose. Do not administer doses below 2.5 mg. For myelodysplastic syndromes: starting dose is 10 mg/day—if neutropenia develops within 4 wk of starting at a 10 mg/day dose in a patient with a baseline neutrophil count (ANC) ≥1000/mcL and ANC falls to <750/mcL interrupt lenalidomide therapy and resume at 5 mg/day dose when ANC returns to ≥1000/mcL. If baseline ANC is <1000/mcL and ANC falls to <500/mcL, interrupt therapy and resume at 5 mg/day dose when ANC returns to ≥500/mcL. If neutropenia develops after 4 wk of therapy at 10 mg/day dose, and ANC <500/mcL for ≥7 days or <500/mcL associated with fever ≥38.5°C, interrupt therapy and resume at 5 mg/day when ANC returns to ≥500/mcL. If neutropenia develops at 5 mg/day dose and ANC <500/mcL for ≥7 days or <500/mcL associated with fever ≥38.5°C, interrupt therapy and resume at 2.5 mg daily when ANC returns to ≥500/mcL. For mantle cell lymphoma: starting dose is 25 mg/day on days 1–21 of repeated 28-day cycles—If neutrophils fall to <1000/mcL for at least 7 days or fall to <1000/mcL with fever ≥38.5°C or fall to <500/mcL, interrupt therapy and follow CBC weekly. If neutrophils return to ≥1000/mcL resume at 5 mg less than previous dose. Do not administer doses below 5 mg. For marginal zone lymphoma or follicular lymphoma: If neutrophils <1000/mcL for at least 7 days OR <1000/mcL with associated temperature at least 38.5° C OR <500/mcL hold lenalidomide and follow with weekly CBC. If neutrophils return to ≥1000/mcL and patient starting dose was 20 mg daily, resume at 5 mg less than previous dose. Do not administer doses below 5 mg. If neutrophils return to ≥1000/mcL patient starting dose was 10 mg daily, resume at 5 mg less than previous dose. Do not administer doses below 2.5 mg.
  • May cause thrombocytopenia with an onset of 28 days (range 8–290 days) and a recovery in 22 days (range 5–224 days). For multiple myeloma: starting dose is 25 mg/day—If platelets fall to <30,000/mcL interrupt therapy and follow CBC weekly. When platelets return to ≥30,000/mcL restart lenalidomide at next lower dose. For each subsequent drop <30,000/mcL interrupt therapy. When platelets return to ≥30,000/mcL resume at next lower dose. Do not administer doses below 2.5 mg. For myelodysplastic syndrome: starting dose is 10 mg/day—If thrombocytopenia develops within 4 wk of starting a 10 mg dose in a patient with a baseline of ≥100,000/mcL, and platelets fall to <50,000/mcL interrupt lenalidomide therapy and resume at 5 mg/day dose when platelets return to >50,000/mcL. If baseline was <100,000/mcL and platelets fall to 50% of baseline value interrupt therapy. If baseline ≥60,000/mcL and returns to ≥50,000/mcL or if baseline is <60,000/mcL and returns to ≥30,000/mcL resume therapy at 5 mg/day. If thrombocytopenia develops after 4 wk of treatment at 10 mg/day and platelets are <30,000/mcL or <50,000/mcL with platelet transfusions, interrupt therapy. When platelets return to ≥30,000/mcL without hemostatic failure resume therapy at 2.5 mg/day. For mantle cell lymphoma: starting dose is 25 mg/day on days 1–21 of repeated 28–day cycles—If platelets fall to <50,000/mcL interrupt therapy and follow CBC weekly. If platelets return to ≥50,000/mcL resume at 5 mg less than previous dose. Do not administer doses below 5 mg. For follicular lymphoma or marginal cell lymphoma: if platelets <50,000/mcL, hold lenalidomide and follow with weekly CBC. When platelets return to ≥50,000/mcL, if starting dose was 20 mg daily, resume lenalidomide at 5 mg less than the previous dose. Do not dose below 5 mg daily. If starting dose was 10 mg daily, resume at 5 mg less than previous dose. Do not dose below 2.5 mg daily.
  • Monitor liver enzymes periodically during therapy. Stop therapy if enzymes are elevated; may resume when return to normal or decrease dose.
  • May cause anemia and leukopenia.
  • May cause hypokalemia, hypomagnesemia, and ↑ ALT levels.
  • Monitor thyroid function before starting and periodically during therapy.